Introduction The aim of this study was to analyze the differences in diabetic ketoacidosis (DKA) between type 2 diabetes (T2D) and type 1 diabetes (T1D) in a Spanish cohort. Materials and methods This retrospective cohort study included all cases of DKA between 2010 and 2024 in a Spanish tertiary hospital. Clinical and laboratory variables were collected to identify differences between DKA in T2D and T1D. Logistic regression models were used to evaluate 30-day mortality following a DKA event. Results A total of 249 subjects (52.2% female) with a mean age of 50.2 ± 19.9 years were included. Eighty-nine patients (35.7%) had T2D, and 160 (64.3%) had T1D. A higher proportion of cardiovascular precipitating events was observed in the T2D group (12.5% vs. 3.2%; P=.005), along with a more favorable blood gas profile, characterized by higher pH, bicarbonate levels, and lower ketone body concentrations (P<.05). However, 30-day mortality was 13.5% in T2D and 1.3% in T1D (P<.001). Logistic regression models identified cardiovascular events, lower Glasgow Coma Scale scores, and higher urea levels as predictors of mortality (P<.05), independent of age and diabetes type. Conclusion DKA in T2D is associated with a higher risk of mortality due to the severity of precipitating factors, despite a more favorable blood gas profile compared to T1D. Early identification of episodes is essential to prevent complications.